Purpose: Phosphocreatine (PCr) is an essential marker of muscle metabolism, and accurate quantification of its (fs) and its exchange rate (ksw) is essential for diagnosing various muscular and neuromuscular diseases. Although chemical exchange saturation transfer (CEST) MRI can detect the saturation transfer effect from PCr, quantification of the underlying PCr fs and ksw, particularly at low fields, remains challenging due to significant overlapping confounding effects in tissues when using conventional fitting approaches. Deep learning (DL) presents a promising alternative, yet traditional DL models often struggle to capture subtle PCr-specific variations induced by changes in fs or ksw. Furthermore, these models are typically trained on either fully synthetic data, which may not adequately mimic tissues, or in vivo data which lack ground truth.
Methods: This study introduces a global-local two-branch DL model to effectively eliminate confounding effects and capture subtle variations in the PCr CEST effect. Furthermore, our model was trained on partially synthetic data that offers both simulation flexibility and fidelity. Model accuracy was evaluated by using both digital and physical phantoms, and the model was applied to skeletal muscle of healthy rats and rats with amyotrophic lateral sclerosis (ALS).
Results: Phantom experiments demonstrate that our approach surpasses all fitting methods, the state-of-the-art model, and other combinations of DL models and training data. In vivo, the model identified a significant reduction in PCr fs in ALS rats, which other methods fail to detect.
Conclusions: Our global-local two-branch DL model trained using partially synthetic data enhances PCr quantification in skeletal muscle.
Keywords: amyotrophic lateral sclerosis; chemical exchange saturation transfer; deep learning; phosphocreatine.
© 2026 The Author(s). Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.